Promising results of an anti-CCR4 antibody, KW-0761, for relapsed Adult T-Cell Leukemia-Lymphoma (ATL)

Abstract

Introduction: ATL is a distinct T-cell malignancy associated with HTLV-1, carrying a poor prognosis. ATL, as well as other peripheral T-cell lymphomas (PTCLs), is characterized by its cell surface expression of CC chemokine receptor 4 (CCR4), to which KW-0761, a defucosylated, humanized antibody with enhanced ADCC, binds. In a phase I study in patients (pts) with CCR4+ATL and PTCL, encouraging efficacy of KW-0761 (ORR of 31%; 2CRs and 3PRs) was observed (JCO 2010;28:1591). Here, we report the result of a pivotal phase II study of KW-0761 in pts with CCR4+ relapsed ATL. Methods: A multicenter phase II study of KW-0761 has been conducted for pts with CCR4+, relapsed ATL with the primary endpoint being overall response rate (ORR). Responses of disease lesions, progression-free survival (PFS) or overall survival (OS) was also assessed. Pts were planned to receive 8 weekly intravenous infusions of KW- 0761 at 1.0 mg/kg. Objective responses were assessed by an independent efficacy assessment committee. Results: 28 pts were enrolled, among whom, 27 had at least one infusion of KW-0761. Most observed adverse events (AEs) were mild to moderate in severity. 6 pts had severe AEs of skin including 1 Stevens-Johnson syndrome (G3) and 5 skin rashes (G3), all of which were manageable with steroids. Acute infusion reactions were frequently observed, but mostly tolerable. Among the 26 pts evaluable for efficacy, KW-0761 exhibited an ORR of 50% (13/26; 95% CI, 30 to 70), including 8 CRs and 5 PRs, with response rates in each affected lesion being 100% (13/13) for peripheral blood, 63% (5/ 8) for skin, and 25% (3/12) for lymph node disease, respectively. Median PFS and OS were 5 and 14 months, respectively. Updated data will be presented at the meeting. Conclusion: KW-0761 demonstrates definitive activity with acceptable toxicities in pts with CCR4+, relapsed ATL. A multicenter, randomized study of KW-0761 in combination with chemotherapy for untreated ATL pts is ongoing.